Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, 10 Changjiang branch road, Daping, Chongqing, 400042, China.
The Florey Institute, The University of Melbourne, 30 Royal Parade, Parkville, Victoria 3052, Australia.
Nat Rev Neurol. 2017 Sep 29;13(10):612-623. doi: 10.1038/nrneurol.2017.111.
Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becoming more clearly defined. This Review focuses on amyloid-β (Aβ), a major hallmark of AD. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we propose that these abnormal systemic changes might not only develop secondary to brain dysfunction but might also affect AD progression, suggesting that the interactions between the brain and the periphery have a crucial role in the development and progression of AD. Such a systemic view of the molecular pathogenesis of AD could provide a novel perspective for understanding this disease and present new opportunities for its early diagnosis and treatment.
阿尔茨海默病（AD）是最常见的痴呆类型，目前无法治愈；现有的 AD 治疗方法只能适度改善症状。对这种疾病的研究传统上集中在中枢神经系统。然而，现在已经了解到几种外周和全身异常与 AD 有关，我们对这些改变如何导致 AD 的理解也越来越清晰。这篇综述重点关注淀粉样蛋白-β（Aβ），这是 AD 的主要标志之一。我们回顾了与全身异常和 Aβ代谢之间的关联的新发现，并描述了这些关联如何相互作用或反映 Aβ产生和清除的中枢途径。基于这些发现，我们提出这些异常的全身变化不仅可能继发于大脑功能障碍，而且可能影响 AD 的进展，这表明大脑和外周之间的相互作用在 AD 的发展和进展中起着至关重要的作用。AD 的这种系统性分子发病机制观点可以为理解这种疾病提供新的视角，并为其早期诊断和治疗提供新的机会。
